Methods for treating vasomotor symptoms using GABA analogs in a gastric retentive dosage form

Abstract

Methods for treating vasomotor symptoms associated with menopause are described.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority under 35 U.S.C. 119(e) to the U.S. Provisional Application No. 61 / 065,442, filed Feb. 11, 2008, the entire content of which is hereby incorporated by reference.TECHNICAL FIELD[0002]The present subject matter relates to methods of treating a vasomotor symptom using gastric retentive dosage forms comprising a gamma-aminobutyric acid (GABA) analog. In a preferred embodiment, a method for treating one or more menopause-related vasomotor symptoms is provided.BACKGROUND[0003]Vasomotor symptoms of hot flashes, hot flushes, and night sweats are probably best known as being associated with female menopause. These vasomotor symptoms affect an estimated 75% of women aged over 50 years. However, these vasomotor symptoms may also be experienced, for example, by women undergoing breast cancer treatment with the anti-estrogen drug tamoxifen, by women who have had pituitary failure and do not secrete luteinizing hormone a...

AI Technical Summary

Benefits of technology

[0014]In one aspect a method for improving sleep quality in a subject, such as a female subject, experiencing menopause-related vasomotor symptoms by administering a GABA analog, such as gabapentin, pregablin or a prodrug of gabapentin in a gastric retentive dosage form is provided. In some embodiments, sleep quality is measured by the Pittsburgh Quality Sleep Index (PQSI). In some embodiments, administration of gabapentin in a gastric retentive dosage form reduces daytime somnolence in a subject relative to a subject untreated with a gastric retentive dosage form of gabapentin. In some embodiments, a subject treated with a gastric retentive dosage form comprising gabapentin experiences reduced daytime somnolence relative to a subject treated with an immediate release dosage form comprising gabapentin. In some embodiments, the subject is a female.

[0015]In another aspect, a method is provided for improving compliance with gabapentin treatment in a subject experiencing and / or diagnosed with a vasomotor symptom. The method comprises administering gabapentin in a gastric retentive dosage form. In one embodiment, administration of a gastric retentive dosage form comprising gabapentin reduces one or more side effects experienced by a subject associated with an immediate release gabapentin dosage form. In some embodiments, the subject is a female.

[0019]In still another aspect, a dose regimen for treating a female experiencing menopause-related vasomotor symptoms is provided. The method comprises administering a first total daily dose of gabapentin in a gastric retentive dosage form for a first period of time, administering a second total daily dose of gabapentin, wherein the second dose is greater than the first dose, for a second period of time, and administering a third total daily dose for a third period of time, to reduce the frequency and / or severity of vasomotor symptoms.

[0041]In some embodiments, the vasomotor symptom is a hot flash. In one embodiment, the method is effective to delay the onset of a hot flash, reduce the frequency of hot flashes, and / or decrease the severity of hot flashes.

[0045]In some embodiments, a subject being administered a gastric retentive dosage form comprising gabapentin experiences fewer and / or less severe side effects as compared to a subject taking an immediate release dosage form comprising an equivalent dose of gabapentin. In some embodiments, the fewer and / or less severe side effects include one or more side effects selected from somnolence, dizziness, coordination problems, infections, fever, nausea or vomiting, edema, unusual eye movements, double vision or blurred vision, weakness or fatigue, diarrhea or constipation, dry mouth, increased appetite or weight gain, bronchitis, sore throat, mentation, nervousness, speech problems, memory loss, indigestion or heartburn, gas, back pain, problems walking, twitching, high blood sugar, conjunctivitis, ear infection and loss of hearing.

Problems solved by technology

Hot flashes significantly affect the quality of life for those who experience them, and are particularly bothersome at night as they can disturb sleep, leading to fatigue and lack of productivity during the day.

Unfortunately, these hormone therapies are inappropriate for patients previously diagnosed with breast cancer, as either estrogen or progesterone may be associated with an increased risk of cancer recurrence and are known to specifically promote growth of breast cancer cell with estrogen receptors.

Estrogen may also increase the risk of coronary and thromboembolic events during the first year of treatment.

Although the use of low dose estradiol therapy may diminish the risk for these large specialized patient populations, the risks of estrogen therapy are still great.

However, efficacy of these remedies is less than that of the hormone replacement therapies.

), and result in undesired side effects.

More recently, gabapentin use has been associated with the serious side effect of reversible visual field constriction (Bekkelund et al., Brit Med.

In studies involving use of gabapentin to treat menopausal symptoms, the prevalence of somnolence and dizziness side effects resulted in many women discontinuing use of the drug.

The need for t.i.d. dosing and unwanted side effects associated with immediate release gabapentin dosage forms may contribute to poor compliance for some patients in need of relief from vasomotor symptoms.

The above described side effects in this generally healthy population can be a considerable barrier to compliance with gabapentin therapy.

The complexity and length of the titration regimen may result in prematurely discontinuing therapy by patients prior to reaching the maintenance dose or to doctors preferring other therapeutic options.

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